The respiratory system is of prime importance in homeostatic regulation. It is the long range goal of this laboratory to explain the genesis and control of respiratory pattern in terms of the biophysical, synaptic and network properties of identified neurons in the CNS. Determination of the integrative mechanisms by which the CNS produces regulated breathing movements is basic to understanding human physiology and pathophysiology. Development of prophylaxis and treatment of such diseases as sudden infant death syndrome, apnea of prematurity, central alveolar hypoventilation and other forms of respiratory failure will be greatly aided by such knowledge. This proposal addresses two fundamental problems in the neural control of breathing in mammals. I - Where and how is respiratory rhythm generated. We propose a series of neuroanatomical and neurophysiological experiments that seek to define the location(s) of the respiratory oscillator. II - What are the sensorimotor mechanisms that underlie the production of the precisely coordinated movements within each breath? We propose a series of neurophysiological studies that will define brainstem and spinal cord mechanisms responsible for this exquisite sensorimotor integration. The major goals of the proposed grant include: I - Rhythm Generation: (i) identify brainstem sites that may be involved in generation of respiratory rhythm, and (ii) if i suggests a site involved in respiratory rhythm generation, we will classify and study the intrinsic properties of its constituent neurons. II - Sensorimotor Integration: (i) study the central processing of pulmonary stretch receptor and laryngeal nerve afferent activity that affects timing of inspiration and expiration, and; (ii) study the role of the pontine respiratory group ("pneumotaxic center") in control of respiratory pattern by studying the interaction of central inspiratory and pulmonary stretch receptor activity on its constituent neurons.